Sexual dichotomy of an interaction between early adversity and the serotonin transporter gene promoter variant in rhesus macaques

Abstract

A polymorphism in the human serotonin transporter gene promoter (5-HTTLPR) is associated with anxiety and increased risk for developing depression in the face of adversity. Here, we report that among infant rhesus macaques, an orthologous polymorphism (rh5-HTTLPR) interacts with adversity in the form of peer rearing to influence adrenocorticotropic hormone (ACTH) response to stress and, further, that this interaction is sexually dichotomous. ACTH responses to separation are higher in l͞s than in l͞l males. In females, however, it is only among those with a history of adversity that the s allele is associated with increased ACTH responses to stress. Of interest, peer-reared animals, in particular females carrying the s allele, also exhibit lower cortisol responses to stress, a pattern that has been recognized in association with certain stress-related neuropsychiatric disorders. By extension, our findings suggest the intriguing possibility that human females carrying the 5-HTTLPR s allele could be more vulnerable to the effects of early adversity. This interactive effect may underlie the increased incidence of certain stress-related disorders in women.

Variation at the mu-opioid receptor gene (OPRM1) influences attachment behavior in infant primates

“…Notably, frequency-based association studies have a limited power to detect effect sizes at this level, and therefore require considerably larger sample sizes (24). Our study adds to a line of experimental studies in humans and nonhuman primates (25)(26)(27)(28) …”

“…This indicates that two randomly selected macaques would share only 1.45% of their genes by descent (approximately equivalent to a degree of relationship that is observed between second cousins once removed and third cousins). This demonstrates that most pairs of individuals have a low degree of relationship, approximating that observed in some human populations of study (27). To corroborate this for the present study, and exclude a possible confound of relatedness, we analyzed eight additional, functionally unrelated markers, six of which had a comparable number of animals genotyped.…”

“…Several studies have demonstrated that cases exist in which genetic variants that are functionally similar to those that exist in humans are present in macaques (15,18,27,29). This affords us the opportunity to examine how genetic variation may influence complex behavioral traits in subjects living in a controlled environment (30).…”

Interaction between a functional MAOA locus and childhood sexual abuse predicts alcoholism and antisocial personality disorder in adult women

“…Early life traumatic events occurring during a period of neuronal plasticity have been shown in both humans and animal models to determine long-lasting neuroendocrine changes that induce hypersensitivity of the hypothalamic-pituitary-adrenal (HPA) axis to new stressors. [38][39][40] In humans, CSA appears to cause persistent hyperreactivity of both the HPA axis and autonomic system. 38 Furthermore, adverse experiences early in life cause structural changes in the brain.…”

Familial Risk for Mood Disorder and the Personality Risk Factor, Neuroticism, Interact in Their Association with Frontolimbic Serotonin 2A Receptor Binding

“…However, as this study was not designed to detect gender by risk interactions, this finding will need to be replicated in a more focused design. If sustained, this may reflect gender-specific differences in genetic vulnerability to environmental stress (Barr et al, 2004a;Brummett et al, 2007).…”